Effects of Chenodeoxycholate and a Bile Acid Sequestrant, Colesevelam, on Intestinal Transit and Bowel Function

Background & Aims

Di-α hydroxy bile salt, sodium chenodeoxycholate (CDC), and bile acid binding have unclear effects on colonic transit in health and disease.

Methods

We performed 2 randomized, double-blind, placebo-controlled studies. In healthy volunteers (20 per group), we evaluated the effects of oral placebo, 500 mg, or 1000 mg of CDC (delayed-release, each given for 4 days) on gastrointestinal and colonic transit. A second trial compared the effects of colesevelam (1.875 g, twice daily) versus placebo in 24 patients (12 per group) with diarrhea-predominant irritable bowel syndrome (IBS-D) on transit, daily bowel frequency and consistency, and colonic mucosal permeability. Serum fasting 7α-hydroxy-4-cholesten-3-one (7αC4) was measured to screen for bile acid malabsorption. Effects of treatments on transit were compared using analysis of covariance with body mass index and 7αC4 as covariates.

Results

In healthy volunteers, CDC significantly accelerated colonic transit (at 24 and 48 hours, P = .01 and P < .0001, respectively), increased stool frequency and ease of passage (both P < .001), and evacuation (P = .02), and decreased stool consistency (P < .001). Four of the 24 IBS-D patients had increased serum 7αC4 levels. In IBS-D, colesevelam modestly affected overall colonic transit (24 h; P = .22). Emptying of the ascending colon took an average of 4 hours longer in patients given colesevelam compared with placebo; treatment effect was associated with baseline serum 7αC4 levels (P = .0025). Colesevelam was associated with greater ease of stool passage (P = .048) and somewhat firmer stool consistency (P = .12). No effects on mucosal permeability or safety were identified.

Conclusions

Sodium chenodeoxycholate in health and colesevelam in IBS-D patients have opposite effects on colonic transit and fecal parameters.

Abbreviations used in this paper: AC, ascending colon, ANCOVA, analysis of covariance, BAM, bile acid malabsorption, BMI, body mass index, CDC, sodium chenodeoxycholate, FGF-19, fibroblast growth factor 19, IBS-D, diarrhea-predominant irritable bowel syndrome, 7αC4, 7α-hydroxy-4-cholesten-3-one, SCL-90, Submission Checklist 90, t1/2, 50% emptying time